The long-term goal of this research is an understanding of how hormones alter cyclic AMP metabolism in cells and the consequences which follow such changes. We will focus upon and extend our studies with the highly differentiated human lung fibroblast WI-38 and its SV-40 transformed counterpart, WI-38-VA13-2RA (VA13). Specifically, we propose to exploit the two cell strains, which have very different control properties, so as to be able to determine the relative and absolute contributions of the adenyl cyclase system, cyclic nucleotide phosphodiesterase activities, cyclic AMP escape, cyclic GMP metabolism, and other factors to the changes in cyclic AMP levels engendered by prostaglandins, catecholamines, adenosine, and a variety of pharmacological agents. Likewise, we will determine the relationships between these changes in cyclic AMP and the activities of cyclic AMP dependent protein kinases, phosphorylase, glycogen synthetase, and prostaglandin release in both strains. Further, we will attempt to quantitate cyclic AMP turnover in intact WI-38 and VA13. We will also attempt to identify the factors responsible for changes in the responsiveness of the cell strains to hormones (as expressed by alterations in cyclic nucleotide metabolism), including investigations into the hypothesis that such changes may, at least in part, be involved in viral transformation.